WO2014005421 reports a class of benzodioxole compounds, which have an activity of inhibiting acetylcholinesterase and can be used for treating Alzheimer's disease. Of particular interest in this class of compounds is 6-[2-[1-(2-pyridylmethyl)-4-piperidinyl]ethyl]spiro[[1,3]dioxolo[4,5-f]isoindole-7,1′-cyclopropane]-5-one phosphate, with a code of AD-35, chemical structure thereof is shown in Formula I below:

AD-35 is a relatively weak acetylcholinesterase inhibitor, the activity of inhibiting acetylcholinesterase in vitro of AD-35 is about one-tenth of the activity of donepezil. However, this compound shows comparable efficacy to that of donepezil in the Morris water maze test, that is, the effect of improving memory and learning ability thereof is comparable to that of donepezil. This shows that AD-35 is likely to produce effects of improving memory and learning ability through other mechanisms in vivo. Further studies using a rat model of Alzheimer's disease induced by Aβ25-35 found that AD-35 can significantly inhibit the production and release of the pro-inflammatory cytokines TNF-α and IL-1β, thereby greatly reduces the toxicity of Aβ25-35 to nerve cells, and protects nerve cells effectively.
In addition, AD-35 also exhibits a certain ability to chelate transition metal ions such as Cu2+ in vitro, while Cu2+ can accelerate the formation of Aβ fibers and enhance the toxicity of Aβ to nerve cells, thereby promotes the death of nerve cells. Therefore, excessive Cu2+ in brain is also believed to be one of the risk factors for Alzheimer's disease (Sarell et al. J. Biol. Chem. 2010, 285(53), 41533). In view of chemical structure, two nitrogen atoms respectively in the piperidine ring and pyridine ring in AD-35 molecule constitute a structural unit similar to ethylenediamine, which could explain why this compound can chelate transition metal ions to some extent. In terms of safety of a compound, acute toxicity test in mice shows that AD-35 is much less toxic than donepezil. The recent Phase 1 Clinical Single Ascending Dose study (SAD) indicated that subjects did not develop adverse reactions by taking 90 mg of AD-35 in a single dose, which indicates that the compound has a favorable safety.
In summary, AD-35 is promising to be a new drug for treating Alzheimer's disease with minor side effects. Its multiple mechanism of action is likely to make this compound not only alleviate the symptoms of Alzheimer's patients, but also delay the progression of this disease.
Since the synthesis route for preparing AD-35 and analogs thereof reported in WO2014005421 is too long, the operation is complicated, the yield is low, and some steps are not applicable to industrial production, it is necessary to develop a new process route to overcome the existing problems of the preparation method above.